Adaptive changes in postsynaptic dopamine receptors despite unaltered dopamine dynamics in mice lacking monoamine oxidase B

Monoamine oxidase (MAO) B is considered a key enzyme in dopamine metabolism . The present studies, conducted in MAO B knockout mice, show that lack of MAO B does not alter extracellular levels of dopamine in striatum. Similarl y, the synthesis, storage, uptake, and release of dopamine are also unalter ed. However, autoradiography revealed a significant up-regulation of the D2 -like dopamine receptors in the striatum of MAO B knockout mice. Mutant mic e also exhibit a functional supersensitivity of D1-dopamine receptors in th e nucleus accumbens. Thus, the agonist SKF 38,393-induced c-Fos immunoreact ivity was significantly increased in knockout mice as compared with wild-ty pe controls. In view of the apparently normal basal dopamine dynamics obser ved in MAO B knockout mice, we hypothesize that a dopamine-independent mech anism underlies adaptations in dopamine receptor function that occur as a c onsequence of MAO B depletion. Finally, these findings suggest that chronic administration of MAO inhibitors, as occurs in the treatment of Parkinson' s disease and depression, may be associated with an increased responsivenes s of CNS neurons to dopamine receptor ligands.